We will utilize CRISPR/CAS9 mediated gene inactivation to identify viability factors required for the growth of NEPC. We initially will screen two PDX NEPC-derived models for loss of guide RNA's within a library enriched for epigenetic modifiers. We will search for NEPC-specific factors by comparing to an adenocarcinoma cell line (LnCaP) as well as publicly available data for other cell lines assayed with the same guide library. To date, organoid lines have been engineered to express CAS9 and are currently being analyzed for function.